Hydrochloric Acid → HCID 18641945, compound

HRID 258092Notes

Reaction equation

HRID 258092 reaction equation
[C:1]([O:4][CH2:5][CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:10][C@@H:9]([NH:24][C:25](=[O:42])[C@@H:26]([NH:34]C(OC(C)(C)C)=O)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:8]1=[O:43])(=[O:3])[CH3:2].C(OCCN1C2C=CC=CC=2C(C2C=CC=CC=2)=N[C@H](NC(=O)[C@@H](NC(OC(C)(C)C)=O)CC2C=CC=CC=2)C1=O)(=O)C.Cl>C(OCC)(=O)C>[C:1]([O:4][CH2:5][CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:10][C@@H:9]([NH:24][C:25](=[O:42])[C@@H:26]([NH2:34])[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:8]1=[O:43])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 57031470HCID 57031470, compoundHCID 57161645HCID 57161645, compound

Product 1

HCID 18641945HCID 18641945, compoundYield 98.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of a mixture (0.7 g) of (3R)-1-(2-acetoxyethyl)-1,3-dihydro-5-phenyl-3-[((2S)-2-tert-butoxycarbonylamino-3-phenylpropanoyl)amino]-2H-1, 4-benzodiazepine-2-one and (3S)-1-(2-acetoxyethyl)-1,3-dihydro-5-phenyl-3-[((2S)-2-tert-butoxycarbonylamino-3-phenylpropanoyl)amino]-2H-1,4-benzodiazepine-2-one in ethyl acetate (20 ml) was introduced hydrogen chloride gas under cooling in an ice-bath with stirring. After the solution was saturated with hydrogen chloride, the mixture was stirred for 30 minutes under the same temperature and for 1 hour at ambient temperature. After removal of the hydrogen chloride by bubbling dried nitrogen gas, the mixture was evaporated under reduced pressure. To the residue was added water and the mixture was neutralized with a saturated aqueous solution of sodium bicarbonate. The mixture was extracted with ethyl acetate twice and the extract was washed with water and dried over magnesium sulfate. Removal of the solvent afforded a mixture (0.57 g) of (3R)-1-(2-acetoxyethyl)-3-[((2S)-2-amino-3-phenylpropanoyl)amino]-1, 3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2-one and (3S)-1-(2-acetoxyethyl)-3-[((2S)-2-amino-3-phenylpropanoyl)amino]-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2-one.

Workup

  1. temperatureunder cooling in an ice-bath
  2. stirringthe mixture was stirred for 30 minutes under the same temperature and for 1 hour at ambient temperature
  3. customAfter removal of the hydrogen chloride
  4. customby bubbling dried nitrogen gas
  5. customthe mixture was evaporated under reduced pressure
  6. additionTo the residue was added water
  7. extractionThe mixture was extracted with ethyl acetate twice
  8. washthe extract was washed with water
  9. dry with materialdried over magnesium sulfate
  10. customRemoval of the solvent

Sources & evidence

ORD record
ord-e37d1779434840ddbc80017534160bff
Source dataset
uspto-grants-1993_11
Patent number
US05264433

Reaction notes

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